Circulating immune complexes and in vitro cell reactivity in paracoccidioidomycosis

Abstract

The severest forms of paracoccidioidomycosis (Pcm) are associated with impaired cell-mediated immunity, a phenomenon that is reversible with therapy. It has been postulated that plasma factors could be responsible for such immune dysfunction. In this report, circulating immune complexes (C1C) were measured by the Raji cell radioimmunoassay (Raji) and by the ~251-C I q binding assay (C 1 q-BA) in sera from 14 patients with either active or inactive forms of Pcm and from 15 healthy controls. The C 1 q-BA revealed significantly elevated levels of CIC in the sera of all but one of the patients. Four of the 8 active (62%) and 2 of the 6 inactive (33%) patients had CIC levels significantly higher than the controls as determined by the Raji test. Significantly increased levels of C1C were detected only in the active patients by the Raji test. The serum of one of the patients, with a generalized infection and depressed lymphocyte responsiveness, was examined and found to contain a factor which depressed the in vitro proliferation of both homologous and normal lymphocytes. We also found that pre-culture of the patients' lymphocytes before stimulation restored their proliferative capacity, and IC were detectable in the culture supernatants. However, the subsequent addition of the patients' serum to such precultured cells did not reinduce the depression. It is suggested therefore, that the depression of T cell responses observed in Pcm is due to the presence of IC which may interact reversibly with the responding cells and/or activate a suppressor cell population whose activity is diminished by preculture.

Paracoccidioidomycosis: an update

“…Sometimes, the concentration of IgG parallels the activities of complement-fixing or -precipitating antibodies detected by gel diffusion (79,214,278). A study to determine the nature of the precipitating antibodies concluded that they are of the IgG class (108 Circulating immune complexes in paracoccidioidomycosis patients were first described by Arango et al (9) and later confirmed by Chequer-Bou-Habib et al (68,69 6,1993 to prepare, long shelf life, specific (no cross-reactions), reproducible, sensitive, reliable, and reactive in more than one serological test. Different antigen preparations vary greatly in quality, depending on fungal strain, morphological phase, culture medium, size of inoculum, incubation time, and recovery techniques (242,290).…”

“…6,1993 Antigenemia. The description of immune complexes in patients with paracoccidioidomycosis (9,68,69) and the observation of precipitin lines occurring between serum samples set up in the immunodiffusion and counterimmunoelectrophoresis systems suggested for the first time that there was circulating antigen in patient sera (280). Subsequently, attempts have been made to diagnose this mycosis by detecting circulating antigens in serum samples.…”

“…A strong argument in support of this hypothesis is that impairment of cell-mediated responses is reversible by successful therapy (197,264). The search for a factor(s) responsible for negative immunoregulation of cellular immunity during paracoccidioidomycosis has ranged from unidentified inhibitory factors in patient plasma (208,264) and immune complexes (9,68,69,304) to an imbalance in T-cell subsets (200,204).…”

Therapeutic Administration of KM+ Lectin Protects Mice Against Paracoccidioides brasiliensis Infection via Interleukin-12 Production in a Toll-Like Receptor 2-Dependent Mechanism

“…3,4 It has been reported that a high level of humoral immune response is associated with increased disease dissemination. 5 Conversely, the cell-mediated immune response represents the main mechanism of defense in PCM. 1 Resistance to this mycosis results from the commitment of CD4 ϩ T helper (Th) precursors to the Th1 lineage, 6,7 stimulated by early secretion of interleukin (IL)-12, 8 -10 and followed by sustained secretion of interferon (IFN)-␥.…”

Current Status of Nonculture Methods for Diagnosis of Invasive Fungal Infections

“…It has been known for some time that antigen, in the form of immune complexes, is present in patients with paracoccidioidomycosis (6,38). Antigen detection tests may be more effective than antibody tests for diagnosing paracoccidioidomycosis, particularly in immunocompromised individuals and in those who have previously been exposed to P. brasiliensis (80).…”